The most prevalent ticagrelor adverse effects are bleeding, dyspnea, bradycardia, and, in rare cases, thrombotic thrombocytopenic purpura. Although extremely rare, ticagrelor can cause absolute or profound thrombocytopenia. We present a case of total thrombocytopenia caused by ticagrelor after 4 days of treatment. A male in his 60 s with hypertension, type 2 diabetes mellitus, and dyslipidemia presented with chest pain. A 12-lead electrocardiogram showed sinus rhythm at 80 beats per min, ST-segment elevation, Q waves, and ST depression in V4-V6, indicating inferolateral myocardial infarction. Patient received thrombolytics with prompt administration of aspirin and ticagrelor. Baseline platelet count was 138 × 109/L. A subsequent angiography was performed 10 h later that revealed multivessel disease and the patient deemed a candidate for coronary artery bypass surgery. About 72 h after presentation, he had hematuria and his platelet count dropped to 23 109/L. On repeat testing, a complete blood count indicated platelet counts of 23 × 109 and 9 × 109/µL. A peripheral smear revealed no signs of platelet clumping or schistocytes. As a result, ticagrelor and aspirin were promptly stopped. Six platelet units were transfused. Prior to discharge, the platelet count hit the 50 s and then recovered to baseline. Clopidogrel and aspirin were prescribed for the patient. On outpatient follow-up, no thrombocytopenia was observed. In addition to our patient, we came across two patients in the literature who developed profound thrombocytopenia after being treated with ticagrelor. The timing of ticagrelor-induced thrombocytopenia varied and all patients were treated with platelets transfusion and discontinuation of ticagrelor. No thrombocytopenia was seen thereafter. In conclusion, thrombocytopenia with ticagrelor should be considered when other potential causes of thrombocytopenia have been ruled out.